Robotic Search for Optimal Cell Culture in Regenerative Medicine

Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. The system performed 216 forty-day cell culture experiments, with a total experimentation time of 8,640 days. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that by the pre-optimized culture in terms of pigmented scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research. ### Competing Interest Statement G.N.K., T.K., M.K., K.M., and T.N. are employees, executives, or stakeholders of Robotic Biology Institute Inc., which may benefit financially from the increased scientific use of LabDroid Maholo. T.T., C.T.W., T.H., S.H., T.S., Y.O., and K.T. are employees, shareholders, or stakeholders of Epistra Inc., which may benefit financially from the increased scientific use of developed software. All other authors declare no competing interests.